tucatinib plus trastuzumab in patients with her2+ colorectal cancer

Conditions: Metastatic Colorectal Adenocarcinoma

Summary: this trial studies how well the drug tucatinib works when given with trastuzumab and when given by itself. the participants in this trial have her2-positive (her2+) metastatic colorectal cancer (mcrc). 'metastatic' means that the cancer has spread to other parts of the body. in the first part of this study, participants enrolled into cohort a and received both tucatinib and trastuzumab. in the second part of this study, participants are randomly assigned to either cohort b or cohort c. participants in cohort b will receive tucatinib and trastuzumab. participants in cohort c will receive tucatinib. participants in cohort c who do not respond to therapy may have an option to receive tucatinib plus trastuzumab.


Eligibility criteria:
inclusion criteria * histologically and/or cytologically documented adenocarcinoma of the colon or rectum that is metastatic and/or unresectable * unless contraindicated, participants must have received and failed regimens containing the following agents: fluoropyrimidine (e.g., 5-fluorouracil or capecitabine), oxaliplatin, irinotecan, an anti-vegf monoclonal antibody (bevacizumab, ramucirumab, or ziv-aflibercept), and an anti-pd-(l)1 therapy (nivolumab or pembrolizumab) if tumor has deficient mismatch repair proteins or is msi-high. * have progression of unresectable or metastatic crc after the last systemic therapy, or be intolerant of last systemic therapy * have ras wild-type in primary or metastatic tumor tissue, based on expanded ras testing * willing and able to provide the most recently available tissue blocks obtained prior to treatment initiation. if archival tissue is not available, then a newly-obtained baseline biopsy of an accessible tumor * have confirmed her2-positive mcrc, as defined by having tumor tissue tested at a clinical laboratory improvement act (clia)-certified or international organization for standardization (iso)-accredited laboratory, meeting at least one of the following criteria: * her2+ overexpression (3+ immunohistochemistry \[ihc\]) by an fda-approved or conformité européene (ce)-marked her2 ich test * her2 2+ ihc is eligible if the tumor is amplified by an fda-approved or ce-marked her2 in situ hybridization assay (fish or chromogenic in situ hybridization \[cish\])) * her2 (erbb2) amplification by clia-certified or iso-accredited next generation sequencing (ngs) sequencing assay * have radiographically measurable disease assessable by recist 1.1, with at least one site of disease that is measurable and that has not been previously irradiated; or, if the participant has had previous radiation to the target lesion(s), there must be evidence of progression since the radiation * eastern cooperative oncology group (ecog) performance status (ps) of 0, 1, or 2 * life expectancy greater than 3 months * have adequate hematological, hepatic, renal, coagulation, and cardiac function exclusion criteria * previous treatment with anti-her2 targeting therapy * previous treatment with any systemic anticancer therapy, non-central nervous system radiation, or experimental agent within 3 weeks of first dose of study treatment * toxicity related to prior cancer therapies that has not resolved to ≤ grade 1, with the following exceptions: * alopecia and neuropathy, which must have resolved to ≤ grade 2 * congestive heart failure (chf), which must have been ≤ grade 1 in severity at the time of occurrence, and must have resolved completely * anemia, which must have resolved to ≤ grade 2 * decreased anc, which must have resolved to ≤ grade 2 * have clinically significant cardiopulmonary disease * have known myocardial infarction, unstable angina, cardiac or other vascular stenting, angioplasty, or cardiac surgery within 6 months prior to first dose of study treatment * major surgical procedure, open biopsy, or significant traumatic injury ≤28 days prior to enrollment (≤56 days for hepatectomy, open thoracotomy, or major neurosurgery) or anticipation of need for major surgical procedure during the study * serious, non-healing wound, ulcer, or bone fracture * known to be positive for hepatitis b by surface antigen expression * known to have active hepatitis c infection * exception for participants with a documented sustained virologic response of 12 weeks * known to be positive for human immunodeficiency virus (hiv) * subjects who are pregnant, breastfeeding, or planning a pregnancy * inability to swallow pills or any significant gastrointestinal disease which would preclude the adequate oral absorption of medications * have used strong cyp2c8 inhibitor within 5 half-lives of the inhibitor, or have used a strong cyp2c8 or cyp3a4 inducer within 5 days prior to first dose of study treatment * history of another malignancy within 3 years before the first dose of study drug, or any evidence of residual disease from a previously diagnosed malignancy. * exceptions are malignancies with a negligible risk of metastasis or death * subjects with known active cns metastasis * irradiated or resected lesions are permitted, provided the lesions are fully treated and inactive, subject is asymptomatic, and no steroids have been administered for at least 30 days

Keywords: her2 erbb2 colorectal cancer seattle genetics